During the past year, we used the binding of mouse uterine and kidney cytosol estradial receptor complexes (E2R) to oligodeoxynueleotide-cellulose to define aspects of the polynucleotide binding domain of the receptors. The findings include the following: 1) receptors can distinguish between the nucleotide bases as well as interact with the polyphosphate backbone of the nucleotide; 2) the order of preference for binding is oligodG greater then oligodT equals oligodC much greater then oligodA much greater then oligodI; 3) the binding to oligodG is more stable to heat, purification, pyridoxal 5 phosphate and cibacron blue inhibition than is the binding to the other nucleotides; 4) binding to the oligodeoxynucleotides of partially purified E2R is stimulated by histones (H2A, H2B and H3) and by a heat stable cytosol protein. We are extending our work on polynucleotide recognition to restriction nuclease fragments of DNA with the goal of identifying high affinity binding sites.